- Email: [email protected]
Readmissions After Mechanical Thrombectomy for Acute Ischemic Stroke in the United States: A Nationwide Analysis
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Readmissions After Mechanical Thrombectomy for Acute Ischemic Stroke in the United States: A Nationwide Analysis TagedPPreethi Ramchand, MD,*,† Dylan P. Thibault, MS,†,‡ James A. Crispo, PhD,† Joshua Levine, MD,*,† Robert Hurst, MD,§ Michael T. Mullen, MD, MS,† Scott Kasner, MD,† and Allison W. Willis, MD, MS†,‡,||,{,# TagedP
Objective: Mechanical thrombectomy after acute ischemic stroke has been shown to improve clinical outcomes. Data on short-term hospitalization outcomes after thrombectomy are needed. Our objective was to quantify 30- and 90-day readmissions after thrombectomy and identify factors associated with readmissions. Methods: Retrospective observational analysis of adult patients hospitalized between January and November 2014, using data from the 2014 Nationwide Readmissions Database. Readmission rates were calculated and examined according to patient, clinical, and hospital characteristics using descriptive statistics. Weighted unconditional logistic regression models estimated the odds of readmission and examine the associations between select characteristics and readmission. Results: 4850 individuals who underwent mechanical thrombectomy for acute ischemic stroke in 2014 were eligible for 30-day readmissions analyses. The nonelective readmission rate was 12.5% at 30 days, 20.7% at 90 days. Sepsis and stroke were the most common reasons for readmission. Female sex (adjusted odds ratio [AOR] 1.34, 1.02-1.77 at 30 days), discharge to inpatient postacute care facility (AOR 1.61, 1.07-2.41 at 30 days, AOR 1.99, 1.47-2.69 at 90 days), and longer initial length of stay (AOR 1.52, 1.04-2.23 at 30 days, AOR 1.67, 1.14-2.43 at 90 days) were associated with a higher likelihood of readmission. Thrombectomy complications were rare and not associated with readmission. Conclusions: 1 in 8 thrombectomy patients had a short-term readmission in 2014. Characteristics suggestive of a complicated hospital course or greater physical disability were the primary predictors of readmission. This study provides preliminary data for evaluations of the public health impact of mechanical thrombectomy in real world settings. TagedPKey Words: Stroke—readmission—mechanical thrombectomy—outcomes © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
From the *Department of Neurocritical Care, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; †Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; ‡Department of Neurology Translational Center of Excellence for Neuroepidemiology and Outcomes Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; §Department of Neuroradiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; ||Department of Biostatistics Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania; {Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and #Leonard Davis Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Received April 23, 2018; revision received May 19, 2018; accepted May 22, 2018. No grant support. Disclosure of Conflict of Interest: All authors declare that there is no conflict of interest. Address correspondence to Preethi Ramchand, MD, Hospital of the University of Pennsylvania, Department of Neurocritical Care, 3 West Gatesm 3400 Spruce Street, Philadelphia, PA 19104. E-mail: [email protected] 1052-3057/$ - see front matter © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.035
Journal of Stroke and Cerebrovascular Diseases, Vol. &&, N0. && (&&), 2018: pp 1-9
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Introduction TagedPStroke is a leading cause of death and disability in the United States. There are an estimated 795,000 new and recurrent strokes diagnosed each year, with nearly $34 billion in direct and indirect costs.1 Consequently, substantial public and private research investments have focused on stroke prevention and acute stroke treatment. TagedPAcute ischemic stroke (AIS) management was first revolutionized over 20 years ago with the introduction of intravenous recombinant tissue plasminogen activator.2 However, the benefits of intravenous recombinant tissue plasminogen activator have been limited by its efficacy in vessel recanalization and geographic disparities in its utilization.3-5 TagedPMotivated by the limits of rt-PA effectiveness, other therapeutic adjuncts for acute ischemic stroke have been developed. Endovascular thrombectomy has emerged as a “game changing” intervention, because of higher rates of vessel recanalization and the ability to treat up to 24 hours. Eight recent randomized controlled trials (RCTs) have demonstrated an outcome benefit with mechanical thrombectomy in acute stroke.6-13 As a result, the use of thrombectomy has been steadily increasing, with some estimates suggesting that one in ten patients with acute stroke will be eligible for intervention in the foreseeable future.14 TagedPRCTs are central to establishing efficacy but have limited generalizability. Studies that examine the use of a new medical treatment in the general population, particularly one that requires advanced infrastructure and personnel training, are needed to establish acceptable thresholds for real-world outcomes. Immediate outcomes after thrombectomy including recurrent stroke, hospital length of stay (LOS), and discharge disposition, have been studied on a multisystem level with the use of administrative datasets.15 However, the rates and causes of hospital readmissions after thrombectomy for AIS remain unknown. TagedPThe National Readmissions Database (NRD) contains all payer inpatient stays occurring in 22 participating states across the United States and provides a unique opportunity to examine population level outcomes after thrombectomy for stroke. We used the NRD to quantify and characterize readmissions in this population. Specific goals were (1) to describe patients undergoing thrombectomy for AIS in the United States and the outcomes associated with the initial hospitalization (2) to quantify 30and 90-day readmissions after thrombectomy and (3) examine patient, clinical, and hospital factors associated with readmission after thrombectomy.
Materials and Methods Ethics Statement TagedPThe research was approved by the University of Pennsylvania Institutional Review Board.
Data Source TagedPThe study was conducted using administrative health data from the 2014 NRD. Sponsored by the Agency for Healthcare Research and Quality (AHRQ), the NRD is part of the Healthcare Cost and Utilization Project (HCUP), which has produced a family of databases to support national health care utilization analyses. Available data include health service utilization information for all health insurance payer categories in the United States, including the uninsured. The NRD contains demographic, clinical, and hospital data that may be weighted to generate nationally representative estimates of hospitalizations and subsequent readmissions. Inpatients in the NRD datasets may be tracked longitudinally within but not across calendar years.16 The NRD does not contain race/ethnicity data or allow for cluster analyses at the hospital level or examinations of the relationships between hospital procedural volume and outcome.
Study Population TagedPThe 2014 NRD was queried to identify adults (ages 18 and older) with index hospital stays for mechanical thrombectomy and ischemic stroke. An index hospitalization was defined as a hospitalization in which the primary discharge diagnosis (identified using International Classification of Diseases, Ninth Revision, ICD-9 classification) was ‘acute ischemic stroke’ (ICD-9 codes-433, 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434,434.01, 434.11, 434.91, 436, 437, 437.1),17 a procedure code for mechanical thrombectomy (39.74) was recorded,18 and the patient was discharged alive. As it is not possible to track individuals in the NRD across state borders, index admissions that occurred outside a patient's home state were excluded. To ensure that all readmissions could be identified, index encounters discharged on/after December 1 and October 1 were excluded from 30- and 90 -day readmission analyses, respectively.
Individual, Clinical and Hospital Characteristics TagedPDemographic and clinical data extracted from the index thrombectomy admission included patient age, sex, health insurance payer category, median household income in the patient's zip code, hospital LOS, and discharge disposition. Comorbidities were categorized using the ICD-9based Elixhauser comorbidity measures, which have been validated in administrative claims data.19 A single overall inpatient Elixhauser comorbidity score was computed by summing the number of distinct comorbidities. TagedPWe examined hospital characteristics of the index admission including hospital size and control/ownership. In preliminary analyses, we found that teaching status and urban location were highly correlated in the NRD, therefore we chose to use the teaching status variable and
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TagedPdid not include additional NRD variables for population density in our analyses. TagedPWe created indicator variables to examine specific potential complications of mechanical thrombectomy: groin hematoma (ICD-9 code 998.12) and vessel dissection (ICD-9 codes 443.2, 443.29).20 Notably, symptomatic intracerebral hemorrhage was not examined, as prior studies suggest ICD-9 coding for this diagnosis is not reliable.21
Readmissions TagedPReadmission time frames of 30 and 90 days were chosen because they are commonly used readmission windows for performance metrics. Time to readmission was calculated as the number of days between the discharge date of the index encounter and the earliest hospital readmission date. We excluded planned readmissions.
Statistical Analyses TagedPNationally representative estimates of mechanical thrombectomy for AIS 30- and 90-day readmission data were calculated using NRD survey weighting methods and examined according to patient, clinical, and hospital characteristics using descriptive statistics. Principal reasons for readmissions were grouped using the HCUP single-level Clinical Classification Software, a classification scheme that enables individual ICD-9 codes to be classified according to clinical similarities.22 The ten most common principle diagnoses for readmission were reported according to decreasing prevalence. We constructed weighted unconditional logistic regression models to estimate the odds of all-cause nonelective readmissions associated with demographic, clinical, and hospital characteristics. The HCUP Data Use Agreement prohibits the reporting of 10 or fewer observations; details were suppressed in results tables as appropriate. Statistical analyses were performed using SAS v9.4 (SAS Institute Inc., Cary, NC).
Results Cohort Characteristics TagedP4850 patients underwent mechanical thrombectomy during hospitalization with acute ischemic stroke in 2014 that were eligible for 30-day readmission. We detail characteristics of only the cohort eligible for 30-day readmission analyses, as similar data were found for the 90-day readmission cohort. The majority of patients were ages 60 and older; almost a quarter were ages 80 and above (21.6%) (Table 1). Males and females were equally represented (males = 50.9%, females = 49.1%). Over 57% of mechanical thrombectomy patients had Medicare insurance, consistent with an older average age. Almost 90% of thrombectomies occurred at metropolitan teaching hospitals. Less than 1% took place at rural/nonmetropolitan hospitals.
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TagedPVascular risk factors were common among thrombectomy recipients. Hypertension was the most commonly coded pre-existing condition (76.3%). Diabetes was second (21.2%), followed by congestive heart failure (19.1%), chronic obstructive pulmonary disease (13.5%), obesity (14.7%) and valvular disease (6.9%). Other commonly documented pre-existing conditions that are not historically associated with increased risk of included anemias (17.9%), depression (11.4%), peptic ulcer disease (14.0%), and hypothyroidism (12.4%). All other pre-existing conditions detectable by HCUP comorbid disease software were found in less than 10% of thrombectomy recipients. TagedPThe LOS was 1 to 5 days in 31.0%, between 6 and 19 days for 45.5% and greater than 20 days for 23.5% of index stays. Upon discharge, 33.7% of patients were discharged home. 49.9% were discharged to inpatient postacute care, either inpatient rehabilitation or skilled nursing facilities. The remaining 16.3% of patients were discharged home with home health care (Table 1).
Mechanical Thrombectomy Complications and CareRelated Adverse Events TagedPThe most specific potential complications of thrombectomy—vessel dissection (.4%) and groin hematoma (1.5%)—were rare.
Readmissions TagedPThe overall rate of all-cause nonelective readmission at 30 days was 12.5% and at 90 days was 20.7%. Forty one percent of readmissions occurred within the first seven post-discharge days. There was a statistically significant difference in median Elixhauser Comorbidity Index Score between readmitted and those not readmitted (30 days: 4.8 versus 4.3 P = .001; 90 days: 4.8 versus 4.2 P < .001). Median LOS during the index admission was 2 days longer among individuals who were readmitted, 10.8 (interquartile range 5.7-19.3) days versus 8.9 (interquartile range 4.2-18.2) days (P = .006). TagedPAs displayed in Table 2, logistic regression models that accounted for index admission characteristics (Elixhauser index, LOS, discharge disposition, hospital teaching status) and patient characteristics (age, sex, median zip code income, insurance) found that female sex was associated with increased odds of readmission (adjusted odds ratio [AOR] 1.34, 1.02-1.77) at 30 days, but not at 90 days (AOR 1.19, .91-1.55). Compared to routine discharge home, discharge to inpatient postacute care was associated with increased likelihood of readmission (AOR 1.61, 1.07-2.41 at 30 days, AOR 1.99, 1.47-2.69 at 90 days). Compared to discharges that occurred at day 5 or less, LOS from 6 to 19 days was associated with a 52% increase in adjusted odds of readmission at 30 days (AOR 1.52, 1.04-2.23), and 67% greater adjusted odds of readmission at 90 days (AOR 1.67, 1.14-2.43). Index admissions of 20 or more
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Table 1. Baseline characteristics for mechanical thrombectomy for acute ischemic stroke, NRD, 2014 Characteristic
Mechanical thrombectomy inpatients N = 4850 n (%)
Age Median (IQR) <40 40-49 50-59 60-69 70-79 80+ Sex Male Female Primary payer Medicare Medicaid Private insurance Self-pay/no-charge/other Zip-code quartile $1-$37,999 $38,000-$47,999 $48,000-$63,999 $64000+ Control/ownership of hospital Government, nonfederal Private, not-for-profit Private, for-profit Hospital bedsize Small Medium Large Teaching status Metropolitan nonteaching Metropolitan teaching Nonmetropolitan Elixhauser comorbidity index score Median, IQR 0-1 Condition 2 Conditions 3 Conditions 4+ Conditions Common comorbid conditions (>10) Deficiency anemias Congestive heart failure Chronic pulmonary disease Depression Diabetes, uncomplicated Hypertension Hypothyroidism Obesity Valvular disease Potential MT-related complications Groin hematoma Vessel dissection
53.1 (43.2) 282 (5.8) 386 (8.0) 773 (15.9) 1117 (23.0) 1206 (24.9) 1086 (22.4) 2416 (49.8) 2435 (50.2) 2867 (59.1) 468 (9.6) 1194 (24.6) 320 (6.6) 1390 (28.7) 1350 (27.8) 1089 (22.5) 976 (20.1) 771 (15.9) 3758 (77.5) 320 (6.6) 205 (4.2) 490 (10.1) 4155 (85.7) 499 (10.3) 4313 (88.9) * 3.5 (5.9) 171 (3.5) 363 (7.5) 735 (15.2) 3581 (73.8) 887(18.3) 1009 (20.8) 689 (14.2) 548 (11.3) 1033 (21.3) 3689 (76.1) 624 (12.9) 715 (14.7) 706 (14.6) * *
*HCUP DUA limits the public reporting of counts <10. Abbreviations: “Care Related”, misadventures to patients during surgical and medical care; IQR, interquartile range; MT, mechanical thrombectomy; NRD, National Readmissions Database; “Treatment related”, drugs, medicinal and biological substances causing adverse effects in therapeutic use.
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Table 2. Factors associated with 30, 90 day nonelective readmission of persons with mechanical thrombectomy, NRD 2014
Characteristic Age <40 40-49 50-59 60-69 70-79 80+ Sex Male Female Primary payer Medicare Medicaid Private insurance Self-Pay/no-charge/other Zip-code quartile $1-$37,999 $38,000-$47,999 $48,000-$63,999 $64000+ Index stay disposition home /routine Inpatient post-acute care Home with home health care Elixhauser comorbidity score 1 condition 2 conditions 3 conditions 4+ conditions Length of index stay 1-5 days 6-19 days >=20 days Teaching status Metropolitan nonteaching Metropolitan teaching Nonmetropolitan Specific complications Groin hematoma (yes versus no) Vessel dissection (yes versus no)
30-day nonelective readmission rate N (%)
Odds of 30-day readmission AOR (95 CI)
90-day nonelective readmission rate N (%)
Odds of 90-day readmission AOR (95 CI)
45 (16) 29 (7.5) 65 (8.5) 142 (12.7) 156 (13) 167 (15.4)
1.56 (.66-3.72) .72 (.3-1.76) .80 (.44-1.47) 1.09 (.69-1.72) .93 (.65-1.32) Ref.
60 (25.3) 43 (13.4) 117 (18.4) 176 (19.6) 204 (21.1) 216 (24.5)
2.15 (1-4.63) .92 (.39-2.17) 1.3 (.77-2.19) 1.12 (.74-1.69) .94 (.67-1.32) Ref.
253 (10.5) 352 (14.5)
Ref. 1.34 (1.02-1.77)*
357 (18.3) 458 (23)
Ref. 1.19 (.91-1.55)
411 (14.3) 67 (14.4) 108 (9) 19 (5.8)
1.41 (.81-2.44) 1.6 (.90-2.86) Ref. .59 (.25-1.39)
545 (23.5) 83 (22.1) 156 (16) 31 (11.8)
1.56 (.96-2.56) 1.3 (.73-2.33) Ref. .69 (.38-1.24)
182 (13.1) 153 (11.4) 154 (14.1) 107 (10.9)
1.22 (.77-1.95) 1.02 (.64-1.63) 1.42 (.95-2.13) Ref.
232 (20.2) 247 (22.2) 171 (19.2) 157 (20.9)
.93 (.63-1.38) 1.06 (.69-1.6) .92 (.61-1.39) Ref.
135 (8.6) 388 (15.5) 82 (10.6)
Ref. 1.61 (1.07-2.41) 1.14 (.67-1.93)
164 (12.9) 523 (26) 128 (19.9)
Ref. 1.99 (1.47-2.69)* 1.49 (.96-2.3)
13 (7.5) 24 (6.6) 99 (13.5) 469 (13.1)
Ref. .82 (.27-2.5) 1.56 (.59-4.11) 1.28 (.57-2.86)
19 (13.6) 35 (11.2) 125 (20.2) 637 (22.2)
Ref. .74 (.3-1.82) 1.25 (.52-3.02) 1.19 (.57-2.45)
120 (8.4) 329 (14.5) 155 (13.5)
Ref. 1.52 (1.04-2.23)* 1.57 (.99-2.49)
156 (13) 442 (24.3) 217 (23.6)
Ref. 1.67 (1.14-2.43)* 1.73 (1.18-2.53)*
68 (13.6) 533 (12.4) * (9.2)
1.05 (.75-1.47) Ref. .58 (.15-2.29)
86 (21.3) 722 (20.6) * (22.5)
.96 (.72-1.29) Ref. .85 (.19-3.87)
1.04 (.35-3.11) 2.23 (.71-7.03)
13 (18.2) * (39.7)
.86 (.35-2.08) 2.56 (.76-8.67)
* *
*HCUP DUA limits the public reporting of counts < 10. **P < .05. Abbreviations: AOR, adjusted odds ratio; 95 CI, 95% confidence interval; ICH, intracerebral hemorrhage; NRD, National Readmissions Database.
TagedPdays were similarly associated with increased odds of readmission at 90 days (AOR 1.73, 1.18-2.53). There was no statistically significant association between readmission and patient insurance, Elixhauser score, patient income, thrombectomy complications, or discharge home with home health care in our fully adjusted models.
Readmission Diagnoses TagedPThe most common principle diagnoses documented in 30-day readmissions were sepsis (12.4%), stroke (9.9%), complications of medical care (5.5%), cardiac arrhythmias (5.5%), and heart failure exacerbations (5.4%). The most common principle diagnoses documented in 90-day
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Table 3. Principle discharge diagnoses associated with 30 day unplanned readmission after mechanical thrombectomy, NRD 2014 Diagnosis
Number of individuals readmitted
Percent of readmissions
Percent of thrombectomy patients
75 60 33 33 32 27 23 22 17 16 14 14 13 11
12.42 9.99 5.53 5.40 5.33 4.53 3.86 3.69 2.89 2.60 2.39 2.26 2.10 1.79
1.5 1.2 .7 .7 .7 .6 .5 .5 .4 .3 .3 .3 .3 .2
Septicemia Acute cerebrovascular disease Complications of surgical procedures or medical care Cardiac dysrhythmias Congestive heart failure Acute and unspecified renal failure Urinary tract infections Late effects of cerebrovascular disease Gastrointestinal hemorrhage Pulmonary heart disease Rehabilitation care Aspiration pneumonitis Transient cerebral ischemia Complication of device; implant or graft Abbreviation: NRD, National Readmissions Database.
TagedPreadmissions were sepsis (11.8%), stroke (10.2%), cardiac arrhythmias (7.1%), heart failure exacerbations (5.4%), and renal failure (4.4%) (Tables 3 and 4).
Discussion TagedPStroke is a debilitating disease and a common cause of hospitalizations among the elderly. Mechanical thrombectomy has been shown in randomized controlled trials to be safe and effective. However, real world data are limited, which are important to identity actionable care limitations. TagedPWe have begun to address this knowledge gap in what we believe is the first national study of readmission outcomes for mechanical thrombectomy in acute ischemic stroke, with a focus on clinical conditions associated with
rTagedP eadmission. Vahidy et al. identified rates of 30-day readmission for all patients with acute ischemic stroke in 2013, and in subgroup analyses found that patients who underwent recanalization therapy, defined as either intravenous tissue plasminogen activator (IV tPA) or mechanical thrombectomy therapy had lower rates of readmission.23 Most subjects in the recanalization therapy group were treated with IV tPA alone. Our focus on specific causes and predictors of readmission within this population distinguishes our study from this prior work. TagedPWe found that in the United States in 2014, readmission rates after mechanical thrombectomy for stroke were 12.5% and 20.7% at 30 and 90 days, respectively. We also found favorable index hospitalization outcomes, including a low death rate and few thrombectomyrelated complications, supporting RCT data that
Table 4. Principle discharge diagnoses associated with 90 day unplanned readmission after mechanical thrombectomy, NRD 2014 Diagnosis Septicemia Acute cerebrovascular disease Cardiac dysrhythmias Congestive heart failure Acute and unspecified renal failure Urinary tract infections Complications of surgical procedures or medical care Aspiration pneumonitis Gastrointestinal hemorrhage Nonspecific chest pain Complication of device; implant or graft Late effects of cerebrovascular disease Transient cerebral ischemia Pulmonary heart disease Abbreviation: NRD, National Readmissions Database.
Number of individuals readmitted
Percent of readmissions
Percent of thrombectomy patients
96 83 58 44 35 31 30 24 21 19 19 17 17 16
11.8 10.2 7.1 5.4 4.3 3.8 3.7 2.9 2.8 2.6 2.4 2.4 2.1 2.1
2.0 1.7 1.2 .9 .7 .6 .6 .5 .4 .4 .4 .4 .4 .3
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TagedPthrombectomy is safe. Sex, insurance type, discharge destination, and index admission LOS were independent predictors of readmission. TagedPData from prior studies that report a 30-day readmission rate after stroke, regardless of treatment, of 12%-16% and 90-day readmission rate of 19%-30%.24-26 Previously identified causes of both short-and long-term readmissions after ischemic stroke included recurrent stroke, infections (e.g. urinary tract infections, aspiration pneumonia), and worsening of underlying comorbid conditions (e.g. cardiovascular events).27-30 Factors associated with readmission included increasing age, cardiovascular disease (e.g. hypertension, atrial fibrillation, coronary artery disease), prior ischemic stroke, nonhome discharge after the index admission, index admission LOS, premorbid functional status, and initial National Institutes of Health Stroke Scale.31,32 TagedPIn our cohort, septicemia was the most common cause of readmission. Sepsis is a protean diagnosis that has been redefined as recently as 2016.33 Additionally, the validity of coding for sepsis has substantial variability across individual studies, with positive predictive values ranging anywhere from 6% to 100%.34 Therefore the true incidence of sepsis, as defined by current guidelines, may be considerably lower than what our numbers suggest, which may instead refer to any patient who manifests nonspecific signs of infection (e.g. hypotension, low grade fever, encephalopathy, etc.) without a clinical diagnosis of sepsis.35 Nonetheless, prior studies do show a high incidence of poststroke infections. Berger et al. identified sepsis in 12.6% of stroke patients in the acute setting.36 Rates of infection in the acute period after an ischemic stroke have been reported to be as high at 47%, of which 20% are from aspiration pneumonia, likely in the setting of dysphagia, and 20%-24% from urinary tract infections, potentially from indwelling catheters during admission. Urinary tract infections rates remain elevated—16% at 6 months and 22% at 30 months.37,38 The increased risk of poststroke infection, regardless of thrombectomy, underscores the need for comprehensive management of this population. Current preventive measures, such as daily assessments to minimize duration of indwelling catheters and mechanical ventilation, focus on inpatient care. More research is needed to develop systems to reduce infection risk in the outpatient setting as well. TagedPThe second most common reason for hospital readmission at both 30 and 90 days in this population was recurrent stroke, which is also consistent with multiple prior studies of AIS. Recurrent stroke rates at 30 and 90 days, regardless of treatment, have been reported to be anywhere from 3% to 16% and 4% to 20%, respectively.39-41 Risk factors for stroke recurrence include presence of multiple infarcts on index admission, severity of initial stroke, and evidence of large vessel atherosclerosis. Of the recent RCTs comparing thrombectomy to usual care, recurrent stroke at 90 days after thrombectomy was reported in MR
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TagedP LEAN, ESCAPE, and REVASCAT at 5.6%, 4.8%, and C 3.9% respectively,42-44, all of which are lower than our finding of 10.2%. The greater rate in our population may reflect one of a number of possibilities. Firstly, the majority of the thrombectomy RCTs were published after 2014, and improvement in procedural technique combined with better patient selection could have resulted in lower rates of recurrent stroke. Alternatively, it is possible that complication rates are higher in clinical practice than they are in RCTs. Finally, it is possible that heterogeneity of coding for “acute stroke” could overestimate stroke recurrence, if patients are mistakenly assigned a code for acute stroke at readmission based on the index stroke, rather than evidence of a second clinical stroke. TagedPMechanical thrombectomy is a more invasive management strategy than existing acute stroke therapies and may confer a higher risk of adverse outcomes. However, our preliminary data show a low frequency of thrombectomy-associated complications, and no association between procedure-specific complications and readmission in a real world population. These data highlight the potential of thrombectomy to improve outcomes in populations with unmet needs. IV tPA utilization has been shown to be variable, with significant urbanrural discrepancies favoring the former. This has been attributed to a number of different factors, including lack of Primary Stroke Centers availability in rural areas, lower rates of health literacy among rural residents, and barriers to emergency transportation in rural areas.45 Identifying ways to better serve populations with unmet needs should therefore be a priority in the development of mechanical thrombectomy. TagedPIt is important to note that the patient group we have identified in the 2014 NRD predates the publication of clinical trials showing that thrombectomy is beneficial, and likely reflects a highly specific group of patients. Additionally, there was considerable heterogeneity in thrombectomy device utilization in the 2014 population, which has since been refined with subsequent improvement in outcomes since then. As such, this is a preliminary analysis that may not represent current practice but rather represents baseline data for evaluating the potential public health impact of thrombectomy. A future direction that we would like to pursue is incorporation of NRD data from 2015 onward, once that is released, which will likely be more reflective of current practice. TagedPOur study has several limitations. As with any administrative dataset, coding for medical procedures and diagnoses may be inaccurate.46 Although ICD-9 coding algorithms to identify stroke perform well, the accuracy of ICD-9 coding for other outcomes, including mechanical thrombectomy is uncertain.47 Secondly, the NRD lacks specific details about important clinical features of the stroke patient, such as National Institutes of Health Stroke Scale, stroke etiology, and functional status on discharge, which are important outcome predictors. Lastly, certain
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TagedPdata elements were missing on some patients, although this was relatively uncommon. In spite of these limitations, we provide benchmark data on real world outcomes from mechanical thrombectomy for ischemic stroke. Thoughtful dissemination of effective stroke prevention and treatment options are necessary to produce geographic and demographic equitable reductions in stroke burden.
Sources of Funding TagedPDepartment of Neurology Translation Center of Excellence for Neurological Outcomes Research, University of Pennsylvania Perelman School of Medicine
References TagedP 1. Benjamin EJ, Blaha MJ, Chiuve SE. Heart Disease and Stroke Statistics-2017 Update: A Report from the American Heart Association. Circulation 2017 Mar 7;135:e146e603. TagedP 2. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:15811587. TagedP 3. Gonzales S, Mullen MT, Skolarus L, et al. Progressive rural-urban disparity in acute stroke care. Neurology 2017 Jan, 13;88:441-448. TagedP 4. Skolarus LE, Meurer WJ, Shanmugasundaram K, et al. Marked regional variation in acute stroke treatment among medicare beneficiaries. Stroke 2015 Jul;46:1890-1896. TagedP 5. Bhatia R, Hill MD, Shobha N, et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke 2010 Oct;41(10):22542258. TagedP 6. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015 Jan 1;372:11-20. TagedP 7. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015 Mar 12;372:1009-1018. TagedP 8. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015 Mar 12;372:1019-1030. TagedP 9. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015 Jun 11;372:2296-2306. TagedP10. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015 Jun 11;372:2285-2295. TagedP11. Bracard S, Ducrocq X, Mas JL, et al. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol 2016 Oct;15:1138-1147. TagedP12. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018 Jan 4;378:11-21. TagedP13. Albers GW. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018 Feb 22;378:708-718.
TagedP14. Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA 2016 Sep 27;316:1279-1288. TagedP15. Brinjikji W, Rabinstein AA, Kallmes DF, et al. Patient outcomes with endovascular embolectomy therapy for acute ischemic stroke: a study of the national inpatient sample: 2006 to 2008. Stroke 2011 Jun;42:1648-1652. TagedP16. 2014 Introduction to the NRD. Healthcare Cost and Utilization Project (HCUP). December 2016. Agency for Healthcare Research and Quality, Rockville, MD. www. hcupus.ahrq.gov/db/nation/nrd/NRD_Introduction_ 2014.jsp. TagedP17. Andrade SE, Harrold LR, Tjia J, et al. A systematic review of validated methods for identifying cerebrovascular accident or transient ischaemic attack using administrative data. Pharmacoepidemiol Drug Saf 2012;21(Suppl 1):100-128. TagedP18. Qureshi AI, Chaudhry SA, Hassan AE, et al. Thrombolytic treatment of patients with acute ischemic stroke related to underlying arterial dissection in the United States. Arch Neurol 2011 Dec;68:1536-1542. TagedP19. Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD10 administrative data. Med Care 2005 Nov;43:1130-1139. TagedP20. Qureshi AI, Chaudhry SA, Hassan AE, et al. Thrombolytic treatment of patients with acute ischemic stroke related to underlying arterial dissection in the United States. Arch Neurol 2011 Dec;68:1536-1542. TagedP21. Mullen MT, Moomaw CJ, Alwell K, et al. ICD9 codes cannot reliably identify hemorrhagic transformation of ischemic stroke. Circ Cardiovasc Qual Outcomes 2013 Jul;6:505-506. TagedP22. HCUP Clinical Classifications Software (CCS). Healthcare cost and utilization project (HCUP). U.S. Agency for Healthcare Research and Quality, R., MD. Updated March 2017. http://www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp TagedP23. Vahidy FS, Donnelly JP, McCullough LD, et al. Nationwide estimates of 30-day readmission in patients with ischemic stroke. Stroke 2017 May;48:1386-1388. TagedP24. Lichtman JH, Leifheit-Limson EC, Jones SB, et al. Preventable readmissions within 30days of ischemic stroke among medicare beneficiaries. Stroke 2013;44(12 Dec):3429-3435. TagedP25. Moradiya Y, Murthy S, Modi S, et al. Rate and risk factors of recurrent 30-day readmissions following hospitalization for ischemic stroke. In: Platform session “Cerebrovascular Disease and Interventional Neurology; Aug 2015. TagedP26. Lichtman JH, Jones SB, Wang Y, et al. Outcomes after ischemic stroke for hospitals with and without Joint Commission-certified primary stroke centers. Neurology 2011 Jun 7;76:1976-1982. TagedP27. Lin HJ, Chang WL, Tseng MC. Readmission after stroke in a hospital-based registry: risk, etiologies and risk factors. Neurology 2011;76:438-443. TagedP28. Bravata DM, Ho SY, Meehan TP, et al. Readmission and death after hospitalization for acute ischemic stroke: 5-year follow-up in the Medicare population. Stroke 2007;38:1899-1904. TagedP29. Bjerkreim AT, Thomassen L, Brùgger J, et al. Causes and predictors for hospital readmission after ischemic stroke. J Stroke Cerebrovasc Dis 2015;24:2095-2101. TagedP30. Ponomarev D, Miller C, Govan L, et al. Complications following incident stroke resulting in readmissions: an analysis of data from three Scottish health surveys. Int J Stroke 2015 Aug;10:911-917.
ARTICLE IN PRESS READMISSIONS AFTER THROMBECTOMY FOR STROKE TagedP31. Leit~ao A, Brito A, Pinho J, et al. Predictors of hospital readmission 1 year after ischemic stroke. Intern Emerg Med 2017 Feb;12:63-68. TagedP32. Kilkenny MF, Longworth M, Pollack M, et al. Factors associated with 28-day hospital readmission after stroke in Australia. Stroke 2013 Aug;44:2260-2268. TagedP33. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016 Feb 23;315:801-810. TagedP34. Jolley RJ, Sawka KJ, Yergens DW, et al. Validity of administrative data in recording sepsis: a systematic review. Crit Care 2015 Apr 6;19:139. TagedP35. Klompas M, Rhee C. Sepsis and the theory of relativity: measuring a moving target with a moving measuring stick. Crit Care 2016 Nov 21;20:396. TagedP36. Berger B, Gumbinger C, Steiner T, et al. Epidemiologic features, risk factors, and outcome of sepsis in stroke patients treated on a neurologic intensive care unit. J Crit Care 2014 Apr;29(2):241-248. TagedP37. Popović N, Stefanović-Budimkić M, Mitrović N, et al. The frequency of poststroke infections and their impact on early stroke outcome. J Stroke Cerebrovasc Dis 2013 May;22(4):424-429. TagedP38. Langhorne P, Stott DJ, Robertson L, et al. Medical complications after stroke: a multicenter study. Stroke 2000 Jun;31(6):1223-1229. TagedP39. Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med 2016 Apr 21;374(16):1533-1542.
9 TagedP40. Zhong W, Geng N, Wang P, et al. Prevalence, causes and risk factors of hospital readmissions after acute stroke and transient ischemic attack: a systematic review and meta-analysis. Neurol Sci 2016 Aug;37:1195-1202. TagedP41. Mohan KM, Wolfe CD, Rudd AG, et al. Risk and cumulative risk of stroke recurrence: a systematic review and meta-analysis. Stroke 2011 May;42:1489-1494. TagedP42. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015 Jun 11;372(24):2296-2306. TagedP43. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015 Jan 1;372(1):11-20. TagedP44. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015 Mar 12;372:1019-1030. TagedP45. Gonzales S, Mullen MT, Skolarus L, et al. Progressive rural-urban disparity in acute stroke care. Neurology 2017 Jan 31;88:441-448. TagedP46. Woodworth GF, Baird CJ, Garces-Ambrossi G, et al. Inaccuracy of the administrative database: comparative analysis of two databases for the diagnosis and treatment of intracranial aneurysms. Neurosurgery 2009;65:251-256. discussion 256257. TagedP47. Andrade SE, Harrold LR, Tjia J, et al. A systematic review of validated methods for identifying cerebrovascular accident or transient ischemic attack using administrative data. Pharmacoepidemiol Drug Saf 2012 Jan;21 (Suppl 1):100-128.
Readmissions After Mechanical Thrombectomy for Acute Ischemic Stroke in the United States: A Nationwide Analysis TagedPPreethi Ramchand, MD,*,† Dylan P. Thibault, MS,†,‡ James A. Crispo, PhD,† Joshua Levine, MD,*,† Robert Hurst, MD,§ Michael T. Mullen, MD, MS,† Scott Kasner, MD,† and Allison W. Willis, MD, MS†,‡,||,{,# TagedP
Objective: Mechanical thrombectomy after acute ischemic stroke has been shown to improve clinical outcomes. Data on short-term hospitalization outcomes after thrombectomy are needed. Our objective was to quantify 30- and 90-day readmissions after thrombectomy and identify factors associated with readmissions. Methods: Retrospective observational analysis of adult patients hospitalized between January and November 2014, using data from the 2014 Nationwide Readmissions Database. Readmission rates were calculated and examined according to patient, clinical, and hospital characteristics using descriptive statistics. Weighted unconditional logistic regression models estimated the odds of readmission and examine the associations between select characteristics and readmission. Results: 4850 individuals who underwent mechanical thrombectomy for acute ischemic stroke in 2014 were eligible for 30-day readmissions analyses. The nonelective readmission rate was 12.5% at 30 days, 20.7% at 90 days. Sepsis and stroke were the most common reasons for readmission. Female sex (adjusted odds ratio [AOR] 1.34, 1.02-1.77 at 30 days), discharge to inpatient postacute care facility (AOR 1.61, 1.07-2.41 at 30 days, AOR 1.99, 1.47-2.69 at 90 days), and longer initial length of stay (AOR 1.52, 1.04-2.23 at 30 days, AOR 1.67, 1.14-2.43 at 90 days) were associated with a higher likelihood of readmission. Thrombectomy complications were rare and not associated with readmission. Conclusions: 1 in 8 thrombectomy patients had a short-term readmission in 2014. Characteristics suggestive of a complicated hospital course or greater physical disability were the primary predictors of readmission. This study provides preliminary data for evaluations of the public health impact of mechanical thrombectomy in real world settings. TagedPKey Words: Stroke—readmission—mechanical thrombectomy—outcomes © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
From the *Department of Neurocritical Care, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; †Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; ‡Department of Neurology Translational Center of Excellence for Neuroepidemiology and Outcomes Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; §Department of Neuroradiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; ||Department of Biostatistics Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania; {Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; and #Leonard Davis Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Received April 23, 2018; revision received May 19, 2018; accepted May 22, 2018. No grant support. Disclosure of Conflict of Interest: All authors declare that there is no conflict of interest. Address correspondence to Preethi Ramchand, MD, Hospital of the University of Pennsylvania, Department of Neurocritical Care, 3 West Gatesm 3400 Spruce Street, Philadelphia, PA 19104. E-mail: [email protected] 1052-3057/$ - see front matter © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.035
Journal of Stroke and Cerebrovascular Diseases, Vol. &&, N0. && (&&), 2018: pp 1-9
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Introduction TagedPStroke is a leading cause of death and disability in the United States. There are an estimated 795,000 new and recurrent strokes diagnosed each year, with nearly $34 billion in direct and indirect costs.1 Consequently, substantial public and private research investments have focused on stroke prevention and acute stroke treatment. TagedPAcute ischemic stroke (AIS) management was first revolutionized over 20 years ago with the introduction of intravenous recombinant tissue plasminogen activator.2 However, the benefits of intravenous recombinant tissue plasminogen activator have been limited by its efficacy in vessel recanalization and geographic disparities in its utilization.3-5 TagedPMotivated by the limits of rt-PA effectiveness, other therapeutic adjuncts for acute ischemic stroke have been developed. Endovascular thrombectomy has emerged as a “game changing” intervention, because of higher rates of vessel recanalization and the ability to treat up to 24 hours. Eight recent randomized controlled trials (RCTs) have demonstrated an outcome benefit with mechanical thrombectomy in acute stroke.6-13 As a result, the use of thrombectomy has been steadily increasing, with some estimates suggesting that one in ten patients with acute stroke will be eligible for intervention in the foreseeable future.14 TagedPRCTs are central to establishing efficacy but have limited generalizability. Studies that examine the use of a new medical treatment in the general population, particularly one that requires advanced infrastructure and personnel training, are needed to establish acceptable thresholds for real-world outcomes. Immediate outcomes after thrombectomy including recurrent stroke, hospital length of stay (LOS), and discharge disposition, have been studied on a multisystem level with the use of administrative datasets.15 However, the rates and causes of hospital readmissions after thrombectomy for AIS remain unknown. TagedPThe National Readmissions Database (NRD) contains all payer inpatient stays occurring in 22 participating states across the United States and provides a unique opportunity to examine population level outcomes after thrombectomy for stroke. We used the NRD to quantify and characterize readmissions in this population. Specific goals were (1) to describe patients undergoing thrombectomy for AIS in the United States and the outcomes associated with the initial hospitalization (2) to quantify 30and 90-day readmissions after thrombectomy and (3) examine patient, clinical, and hospital factors associated with readmission after thrombectomy.
Materials and Methods Ethics Statement TagedPThe research was approved by the University of Pennsylvania Institutional Review Board.
Data Source TagedPThe study was conducted using administrative health data from the 2014 NRD. Sponsored by the Agency for Healthcare Research and Quality (AHRQ), the NRD is part of the Healthcare Cost and Utilization Project (HCUP), which has produced a family of databases to support national health care utilization analyses. Available data include health service utilization information for all health insurance payer categories in the United States, including the uninsured. The NRD contains demographic, clinical, and hospital data that may be weighted to generate nationally representative estimates of hospitalizations and subsequent readmissions. Inpatients in the NRD datasets may be tracked longitudinally within but not across calendar years.16 The NRD does not contain race/ethnicity data or allow for cluster analyses at the hospital level or examinations of the relationships between hospital procedural volume and outcome.
Study Population TagedPThe 2014 NRD was queried to identify adults (ages 18 and older) with index hospital stays for mechanical thrombectomy and ischemic stroke. An index hospitalization was defined as a hospitalization in which the primary discharge diagnosis (identified using International Classification of Diseases, Ninth Revision, ICD-9 classification) was ‘acute ischemic stroke’ (ICD-9 codes-433, 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434,434.01, 434.11, 434.91, 436, 437, 437.1),17 a procedure code for mechanical thrombectomy (39.74) was recorded,18 and the patient was discharged alive. As it is not possible to track individuals in the NRD across state borders, index admissions that occurred outside a patient's home state were excluded. To ensure that all readmissions could be identified, index encounters discharged on/after December 1 and October 1 were excluded from 30- and 90 -day readmission analyses, respectively.
Individual, Clinical and Hospital Characteristics TagedPDemographic and clinical data extracted from the index thrombectomy admission included patient age, sex, health insurance payer category, median household income in the patient's zip code, hospital LOS, and discharge disposition. Comorbidities were categorized using the ICD-9based Elixhauser comorbidity measures, which have been validated in administrative claims data.19 A single overall inpatient Elixhauser comorbidity score was computed by summing the number of distinct comorbidities. TagedPWe examined hospital characteristics of the index admission including hospital size and control/ownership. In preliminary analyses, we found that teaching status and urban location were highly correlated in the NRD, therefore we chose to use the teaching status variable and
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TagedPdid not include additional NRD variables for population density in our analyses. TagedPWe created indicator variables to examine specific potential complications of mechanical thrombectomy: groin hematoma (ICD-9 code 998.12) and vessel dissection (ICD-9 codes 443.2, 443.29).20 Notably, symptomatic intracerebral hemorrhage was not examined, as prior studies suggest ICD-9 coding for this diagnosis is not reliable.21
Readmissions TagedPReadmission time frames of 30 and 90 days were chosen because they are commonly used readmission windows for performance metrics. Time to readmission was calculated as the number of days between the discharge date of the index encounter and the earliest hospital readmission date. We excluded planned readmissions.
Statistical Analyses TagedPNationally representative estimates of mechanical thrombectomy for AIS 30- and 90-day readmission data were calculated using NRD survey weighting methods and examined according to patient, clinical, and hospital characteristics using descriptive statistics. Principal reasons for readmissions were grouped using the HCUP single-level Clinical Classification Software, a classification scheme that enables individual ICD-9 codes to be classified according to clinical similarities.22 The ten most common principle diagnoses for readmission were reported according to decreasing prevalence. We constructed weighted unconditional logistic regression models to estimate the odds of all-cause nonelective readmissions associated with demographic, clinical, and hospital characteristics. The HCUP Data Use Agreement prohibits the reporting of 10 or fewer observations; details were suppressed in results tables as appropriate. Statistical analyses were performed using SAS v9.4 (SAS Institute Inc., Cary, NC).
Results Cohort Characteristics TagedP4850 patients underwent mechanical thrombectomy during hospitalization with acute ischemic stroke in 2014 that were eligible for 30-day readmission. We detail characteristics of only the cohort eligible for 30-day readmission analyses, as similar data were found for the 90-day readmission cohort. The majority of patients were ages 60 and older; almost a quarter were ages 80 and above (21.6%) (Table 1). Males and females were equally represented (males = 50.9%, females = 49.1%). Over 57% of mechanical thrombectomy patients had Medicare insurance, consistent with an older average age. Almost 90% of thrombectomies occurred at metropolitan teaching hospitals. Less than 1% took place at rural/nonmetropolitan hospitals.
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TagedPVascular risk factors were common among thrombectomy recipients. Hypertension was the most commonly coded pre-existing condition (76.3%). Diabetes was second (21.2%), followed by congestive heart failure (19.1%), chronic obstructive pulmonary disease (13.5%), obesity (14.7%) and valvular disease (6.9%). Other commonly documented pre-existing conditions that are not historically associated with increased risk of included anemias (17.9%), depression (11.4%), peptic ulcer disease (14.0%), and hypothyroidism (12.4%). All other pre-existing conditions detectable by HCUP comorbid disease software were found in less than 10% of thrombectomy recipients. TagedPThe LOS was 1 to 5 days in 31.0%, between 6 and 19 days for 45.5% and greater than 20 days for 23.5% of index stays. Upon discharge, 33.7% of patients were discharged home. 49.9% were discharged to inpatient postacute care, either inpatient rehabilitation or skilled nursing facilities. The remaining 16.3% of patients were discharged home with home health care (Table 1).
Mechanical Thrombectomy Complications and CareRelated Adverse Events TagedPThe most specific potential complications of thrombectomy—vessel dissection (.4%) and groin hematoma (1.5%)—were rare.
Readmissions TagedPThe overall rate of all-cause nonelective readmission at 30 days was 12.5% and at 90 days was 20.7%. Forty one percent of readmissions occurred within the first seven post-discharge days. There was a statistically significant difference in median Elixhauser Comorbidity Index Score between readmitted and those not readmitted (30 days: 4.8 versus 4.3 P = .001; 90 days: 4.8 versus 4.2 P < .001). Median LOS during the index admission was 2 days longer among individuals who were readmitted, 10.8 (interquartile range 5.7-19.3) days versus 8.9 (interquartile range 4.2-18.2) days (P = .006). TagedPAs displayed in Table 2, logistic regression models that accounted for index admission characteristics (Elixhauser index, LOS, discharge disposition, hospital teaching status) and patient characteristics (age, sex, median zip code income, insurance) found that female sex was associated with increased odds of readmission (adjusted odds ratio [AOR] 1.34, 1.02-1.77) at 30 days, but not at 90 days (AOR 1.19, .91-1.55). Compared to routine discharge home, discharge to inpatient postacute care was associated with increased likelihood of readmission (AOR 1.61, 1.07-2.41 at 30 days, AOR 1.99, 1.47-2.69 at 90 days). Compared to discharges that occurred at day 5 or less, LOS from 6 to 19 days was associated with a 52% increase in adjusted odds of readmission at 30 days (AOR 1.52, 1.04-2.23), and 67% greater adjusted odds of readmission at 90 days (AOR 1.67, 1.14-2.43). Index admissions of 20 or more
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Table 1. Baseline characteristics for mechanical thrombectomy for acute ischemic stroke, NRD, 2014 Characteristic
Mechanical thrombectomy inpatients N = 4850 n (%)
Age Median (IQR) <40 40-49 50-59 60-69 70-79 80+ Sex Male Female Primary payer Medicare Medicaid Private insurance Self-pay/no-charge/other Zip-code quartile $1-$37,999 $38,000-$47,999 $48,000-$63,999 $64000+ Control/ownership of hospital Government, nonfederal Private, not-for-profit Private, for-profit Hospital bedsize Small Medium Large Teaching status Metropolitan nonteaching Metropolitan teaching Nonmetropolitan Elixhauser comorbidity index score Median, IQR 0-1 Condition 2 Conditions 3 Conditions 4+ Conditions Common comorbid conditions (>10) Deficiency anemias Congestive heart failure Chronic pulmonary disease Depression Diabetes, uncomplicated Hypertension Hypothyroidism Obesity Valvular disease Potential MT-related complications Groin hematoma Vessel dissection
53.1 (43.2) 282 (5.8) 386 (8.0) 773 (15.9) 1117 (23.0) 1206 (24.9) 1086 (22.4) 2416 (49.8) 2435 (50.2) 2867 (59.1) 468 (9.6) 1194 (24.6) 320 (6.6) 1390 (28.7) 1350 (27.8) 1089 (22.5) 976 (20.1) 771 (15.9) 3758 (77.5) 320 (6.6) 205 (4.2) 490 (10.1) 4155 (85.7) 499 (10.3) 4313 (88.9) * 3.5 (5.9) 171 (3.5) 363 (7.5) 735 (15.2) 3581 (73.8) 887(18.3) 1009 (20.8) 689 (14.2) 548 (11.3) 1033 (21.3) 3689 (76.1) 624 (12.9) 715 (14.7) 706 (14.6) * *
*HCUP DUA limits the public reporting of counts <10. Abbreviations: “Care Related”, misadventures to patients during surgical and medical care; IQR, interquartile range; MT, mechanical thrombectomy; NRD, National Readmissions Database; “Treatment related”, drugs, medicinal and biological substances causing adverse effects in therapeutic use.
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Table 2. Factors associated with 30, 90 day nonelective readmission of persons with mechanical thrombectomy, NRD 2014
Characteristic Age <40 40-49 50-59 60-69 70-79 80+ Sex Male Female Primary payer Medicare Medicaid Private insurance Self-Pay/no-charge/other Zip-code quartile $1-$37,999 $38,000-$47,999 $48,000-$63,999 $64000+ Index stay disposition home /routine Inpatient post-acute care Home with home health care Elixhauser comorbidity score 1 condition 2 conditions 3 conditions 4+ conditions Length of index stay 1-5 days 6-19 days >=20 days Teaching status Metropolitan nonteaching Metropolitan teaching Nonmetropolitan Specific complications Groin hematoma (yes versus no) Vessel dissection (yes versus no)
30-day nonelective readmission rate N (%)
Odds of 30-day readmission AOR (95 CI)
90-day nonelective readmission rate N (%)
Odds of 90-day readmission AOR (95 CI)
45 (16) 29 (7.5) 65 (8.5) 142 (12.7) 156 (13) 167 (15.4)
1.56 (.66-3.72) .72 (.3-1.76) .80 (.44-1.47) 1.09 (.69-1.72) .93 (.65-1.32) Ref.
60 (25.3) 43 (13.4) 117 (18.4) 176 (19.6) 204 (21.1) 216 (24.5)
2.15 (1-4.63) .92 (.39-2.17) 1.3 (.77-2.19) 1.12 (.74-1.69) .94 (.67-1.32) Ref.
253 (10.5) 352 (14.5)
Ref. 1.34 (1.02-1.77)*
357 (18.3) 458 (23)
Ref. 1.19 (.91-1.55)
411 (14.3) 67 (14.4) 108 (9) 19 (5.8)
1.41 (.81-2.44) 1.6 (.90-2.86) Ref. .59 (.25-1.39)
545 (23.5) 83 (22.1) 156 (16) 31 (11.8)
1.56 (.96-2.56) 1.3 (.73-2.33) Ref. .69 (.38-1.24)
182 (13.1) 153 (11.4) 154 (14.1) 107 (10.9)
1.22 (.77-1.95) 1.02 (.64-1.63) 1.42 (.95-2.13) Ref.
232 (20.2) 247 (22.2) 171 (19.2) 157 (20.9)
.93 (.63-1.38) 1.06 (.69-1.6) .92 (.61-1.39) Ref.
135 (8.6) 388 (15.5) 82 (10.6)
Ref. 1.61 (1.07-2.41) 1.14 (.67-1.93)
164 (12.9) 523 (26) 128 (19.9)
Ref. 1.99 (1.47-2.69)* 1.49 (.96-2.3)
13 (7.5) 24 (6.6) 99 (13.5) 469 (13.1)
Ref. .82 (.27-2.5) 1.56 (.59-4.11) 1.28 (.57-2.86)
19 (13.6) 35 (11.2) 125 (20.2) 637 (22.2)
Ref. .74 (.3-1.82) 1.25 (.52-3.02) 1.19 (.57-2.45)
120 (8.4) 329 (14.5) 155 (13.5)
Ref. 1.52 (1.04-2.23)* 1.57 (.99-2.49)
156 (13) 442 (24.3) 217 (23.6)
Ref. 1.67 (1.14-2.43)* 1.73 (1.18-2.53)*
68 (13.6) 533 (12.4) * (9.2)
1.05 (.75-1.47) Ref. .58 (.15-2.29)
86 (21.3) 722 (20.6) * (22.5)
.96 (.72-1.29) Ref. .85 (.19-3.87)
1.04 (.35-3.11) 2.23 (.71-7.03)
13 (18.2) * (39.7)
.86 (.35-2.08) 2.56 (.76-8.67)
* *
*HCUP DUA limits the public reporting of counts < 10. **P < .05. Abbreviations: AOR, adjusted odds ratio; 95 CI, 95% confidence interval; ICH, intracerebral hemorrhage; NRD, National Readmissions Database.
TagedPdays were similarly associated with increased odds of readmission at 90 days (AOR 1.73, 1.18-2.53). There was no statistically significant association between readmission and patient insurance, Elixhauser score, patient income, thrombectomy complications, or discharge home with home health care in our fully adjusted models.
Readmission Diagnoses TagedPThe most common principle diagnoses documented in 30-day readmissions were sepsis (12.4%), stroke (9.9%), complications of medical care (5.5%), cardiac arrhythmias (5.5%), and heart failure exacerbations (5.4%). The most common principle diagnoses documented in 90-day
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Table 3. Principle discharge diagnoses associated with 30 day unplanned readmission after mechanical thrombectomy, NRD 2014 Diagnosis
Number of individuals readmitted
Percent of readmissions
Percent of thrombectomy patients
75 60 33 33 32 27 23 22 17 16 14 14 13 11
12.42 9.99 5.53 5.40 5.33 4.53 3.86 3.69 2.89 2.60 2.39 2.26 2.10 1.79
1.5 1.2 .7 .7 .7 .6 .5 .5 .4 .3 .3 .3 .3 .2
Septicemia Acute cerebrovascular disease Complications of surgical procedures or medical care Cardiac dysrhythmias Congestive heart failure Acute and unspecified renal failure Urinary tract infections Late effects of cerebrovascular disease Gastrointestinal hemorrhage Pulmonary heart disease Rehabilitation care Aspiration pneumonitis Transient cerebral ischemia Complication of device; implant or graft Abbreviation: NRD, National Readmissions Database.
TagedPreadmissions were sepsis (11.8%), stroke (10.2%), cardiac arrhythmias (7.1%), heart failure exacerbations (5.4%), and renal failure (4.4%) (Tables 3 and 4).
Discussion TagedPStroke is a debilitating disease and a common cause of hospitalizations among the elderly. Mechanical thrombectomy has been shown in randomized controlled trials to be safe and effective. However, real world data are limited, which are important to identity actionable care limitations. TagedPWe have begun to address this knowledge gap in what we believe is the first national study of readmission outcomes for mechanical thrombectomy in acute ischemic stroke, with a focus on clinical conditions associated with
rTagedP eadmission. Vahidy et al. identified rates of 30-day readmission for all patients with acute ischemic stroke in 2013, and in subgroup analyses found that patients who underwent recanalization therapy, defined as either intravenous tissue plasminogen activator (IV tPA) or mechanical thrombectomy therapy had lower rates of readmission.23 Most subjects in the recanalization therapy group were treated with IV tPA alone. Our focus on specific causes and predictors of readmission within this population distinguishes our study from this prior work. TagedPWe found that in the United States in 2014, readmission rates after mechanical thrombectomy for stroke were 12.5% and 20.7% at 30 and 90 days, respectively. We also found favorable index hospitalization outcomes, including a low death rate and few thrombectomyrelated complications, supporting RCT data that
Table 4. Principle discharge diagnoses associated with 90 day unplanned readmission after mechanical thrombectomy, NRD 2014 Diagnosis Septicemia Acute cerebrovascular disease Cardiac dysrhythmias Congestive heart failure Acute and unspecified renal failure Urinary tract infections Complications of surgical procedures or medical care Aspiration pneumonitis Gastrointestinal hemorrhage Nonspecific chest pain Complication of device; implant or graft Late effects of cerebrovascular disease Transient cerebral ischemia Pulmonary heart disease Abbreviation: NRD, National Readmissions Database.
Number of individuals readmitted
Percent of readmissions
Percent of thrombectomy patients
96 83 58 44 35 31 30 24 21 19 19 17 17 16
11.8 10.2 7.1 5.4 4.3 3.8 3.7 2.9 2.8 2.6 2.4 2.4 2.1 2.1
2.0 1.7 1.2 .9 .7 .6 .6 .5 .4 .4 .4 .4 .4 .3
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TagedPthrombectomy is safe. Sex, insurance type, discharge destination, and index admission LOS were independent predictors of readmission. TagedPData from prior studies that report a 30-day readmission rate after stroke, regardless of treatment, of 12%-16% and 90-day readmission rate of 19%-30%.24-26 Previously identified causes of both short-and long-term readmissions after ischemic stroke included recurrent stroke, infections (e.g. urinary tract infections, aspiration pneumonia), and worsening of underlying comorbid conditions (e.g. cardiovascular events).27-30 Factors associated with readmission included increasing age, cardiovascular disease (e.g. hypertension, atrial fibrillation, coronary artery disease), prior ischemic stroke, nonhome discharge after the index admission, index admission LOS, premorbid functional status, and initial National Institutes of Health Stroke Scale.31,32 TagedPIn our cohort, septicemia was the most common cause of readmission. Sepsis is a protean diagnosis that has been redefined as recently as 2016.33 Additionally, the validity of coding for sepsis has substantial variability across individual studies, with positive predictive values ranging anywhere from 6% to 100%.34 Therefore the true incidence of sepsis, as defined by current guidelines, may be considerably lower than what our numbers suggest, which may instead refer to any patient who manifests nonspecific signs of infection (e.g. hypotension, low grade fever, encephalopathy, etc.) without a clinical diagnosis of sepsis.35 Nonetheless, prior studies do show a high incidence of poststroke infections. Berger et al. identified sepsis in 12.6% of stroke patients in the acute setting.36 Rates of infection in the acute period after an ischemic stroke have been reported to be as high at 47%, of which 20% are from aspiration pneumonia, likely in the setting of dysphagia, and 20%-24% from urinary tract infections, potentially from indwelling catheters during admission. Urinary tract infections rates remain elevated—16% at 6 months and 22% at 30 months.37,38 The increased risk of poststroke infection, regardless of thrombectomy, underscores the need for comprehensive management of this population. Current preventive measures, such as daily assessments to minimize duration of indwelling catheters and mechanical ventilation, focus on inpatient care. More research is needed to develop systems to reduce infection risk in the outpatient setting as well. TagedPThe second most common reason for hospital readmission at both 30 and 90 days in this population was recurrent stroke, which is also consistent with multiple prior studies of AIS. Recurrent stroke rates at 30 and 90 days, regardless of treatment, have been reported to be anywhere from 3% to 16% and 4% to 20%, respectively.39-41 Risk factors for stroke recurrence include presence of multiple infarcts on index admission, severity of initial stroke, and evidence of large vessel atherosclerosis. Of the recent RCTs comparing thrombectomy to usual care, recurrent stroke at 90 days after thrombectomy was reported in MR
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TagedP LEAN, ESCAPE, and REVASCAT at 5.6%, 4.8%, and C 3.9% respectively,42-44, all of which are lower than our finding of 10.2%. The greater rate in our population may reflect one of a number of possibilities. Firstly, the majority of the thrombectomy RCTs were published after 2014, and improvement in procedural technique combined with better patient selection could have resulted in lower rates of recurrent stroke. Alternatively, it is possible that complication rates are higher in clinical practice than they are in RCTs. Finally, it is possible that heterogeneity of coding for “acute stroke” could overestimate stroke recurrence, if patients are mistakenly assigned a code for acute stroke at readmission based on the index stroke, rather than evidence of a second clinical stroke. TagedPMechanical thrombectomy is a more invasive management strategy than existing acute stroke therapies and may confer a higher risk of adverse outcomes. However, our preliminary data show a low frequency of thrombectomy-associated complications, and no association between procedure-specific complications and readmission in a real world population. These data highlight the potential of thrombectomy to improve outcomes in populations with unmet needs. IV tPA utilization has been shown to be variable, with significant urbanrural discrepancies favoring the former. This has been attributed to a number of different factors, including lack of Primary Stroke Centers availability in rural areas, lower rates of health literacy among rural residents, and barriers to emergency transportation in rural areas.45 Identifying ways to better serve populations with unmet needs should therefore be a priority in the development of mechanical thrombectomy. TagedPIt is important to note that the patient group we have identified in the 2014 NRD predates the publication of clinical trials showing that thrombectomy is beneficial, and likely reflects a highly specific group of patients. Additionally, there was considerable heterogeneity in thrombectomy device utilization in the 2014 population, which has since been refined with subsequent improvement in outcomes since then. As such, this is a preliminary analysis that may not represent current practice but rather represents baseline data for evaluating the potential public health impact of thrombectomy. A future direction that we would like to pursue is incorporation of NRD data from 2015 onward, once that is released, which will likely be more reflective of current practice. TagedPOur study has several limitations. As with any administrative dataset, coding for medical procedures and diagnoses may be inaccurate.46 Although ICD-9 coding algorithms to identify stroke perform well, the accuracy of ICD-9 coding for other outcomes, including mechanical thrombectomy is uncertain.47 Secondly, the NRD lacks specific details about important clinical features of the stroke patient, such as National Institutes of Health Stroke Scale, stroke etiology, and functional status on discharge, which are important outcome predictors. Lastly, certain
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TagedPdata elements were missing on some patients, although this was relatively uncommon. In spite of these limitations, we provide benchmark data on real world outcomes from mechanical thrombectomy for ischemic stroke. Thoughtful dissemination of effective stroke prevention and treatment options are necessary to produce geographic and demographic equitable reductions in stroke burden.
Sources of Funding TagedPDepartment of Neurology Translation Center of Excellence for Neurological Outcomes Research, University of Pennsylvania Perelman School of Medicine
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9 TagedP40. Zhong W, Geng N, Wang P, et al. Prevalence, causes and risk factors of hospital readmissions after acute stroke and transient ischemic attack: a systematic review and meta-analysis. Neurol Sci 2016 Aug;37:1195-1202. TagedP41. Mohan KM, Wolfe CD, Rudd AG, et al. Risk and cumulative risk of stroke recurrence: a systematic review and meta-analysis. Stroke 2011 May;42:1489-1494. TagedP42. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015 Jun 11;372(24):2296-2306. TagedP43. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015 Jan 1;372(1):11-20. TagedP44. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015 Mar 12;372:1019-1030. TagedP45. Gonzales S, Mullen MT, Skolarus L, et al. Progressive rural-urban disparity in acute stroke care. Neurology 2017 Jan 31;88:441-448. TagedP46. Woodworth GF, Baird CJ, Garces-Ambrossi G, et al. Inaccuracy of the administrative database: comparative analysis of two databases for the diagnosis and treatment of intracranial aneurysms. Neurosurgery 2009;65:251-256. discussion 256257. TagedP47. Andrade SE, Harrold LR, Tjia J, et al. A systematic review of validated methods for identifying cerebrovascular accident or transient ischemic attack using administrative data. Pharmacoepidemiol Drug Saf 2012 Jan;21 (Suppl 1):100-128.